Clinical phenotypes and genetic analyses for diagnosis of systemic autoinflammatory diseases in adult patients with unexplained fever
Clinical phenotypes and genetic analyses for diagnosis of systemic autoinflammatory diseases in adult patients with unexplained fever
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DOI：
10.1080/14397595.2020.1784542
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发表时间：
2020-07-22
影响因子：
2.2
通讯作者：
Ida, Hiroaki
中科院分区：
文献类型：
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作者：
Hidaka, Yukiko;Fujimoto, Kyoko;Ida, Hiroaki
目的对不明原因发热患者进行临床和遗传分析，以准确诊断全身性自身炎症性疾病（SAIDs）。方法对179例日本不明原因发热患者的11个aids相关基因的临床表型和基因组变异进行分析。通过下一代测序（NGS）对外显子进行遗传分析，包括外显子-内含子边界。结果3例患者符合非家族性地中海热诊断标准。176例不明原因发热患者中，43例（24.0%）临床诊断为FMF。在搜索除mefv基因外的10个疾病基因变异时，发现53例（30.1%）存在基因变异。其中，最常被发现的基因为enlrp3、NOD2、NLRP12、NLRC4和plcg2，分别占14例、7例、17例、7例和6例。这些变异小于1%的健康个体或新变异，但不被认为是致病的，因为患者不符合临床鉴定的变异引起的saaids的诊断标准。结论在本研究中，24%的日本不明原因发热患者临床诊断为FMF。除mefv外，在30.1%的病例中发现了低频率但非致病性的基因变异。目前尚不清楚这些基因变异在多大程度上导致了炎症表型；因此，进一步的分析将揭示引起发烧的自身炎症表型。
Objective To make an accurate diagnosis of systemic autoinflammatory diseases (SAIDs), clinical and genetic analyses were performed in patients with unexplained fever. Methods The clinical phenotype and genomic variants of 11 genes responsible for SAIDs were analyzed in 179 Japanese patients with unexplained fever. Genetic analysis was performed by next generation sequencing (NGS) on exons including exon-intron boundaries. Results Three cases met the diagnostic criteria for SAIDs other than familial Mediterranean fever (FMF). Considering 176 patients with unexplained fever, 43 cases (24.0%) were clinically diagnosed as FMF. Gene variants were found in 53 cases (30.1%) when searching for variants in the 10 disease genes other than theMEFVgene. Among them, the most frequently-identified genes wereNLRP3,NOD2,NLRP12,NLRC4, andPLCG2, which accounted for 14, 7, 17, 7, and 6 cases, respectively. These variants were less than 1% of healthy individuals or novel variants, but not regarded as pathogenic since the patients did not meet the diagnostic criteria of SAIDs caused by their identified variants clinically. Conclusion Twenty four percent of Japanese patients with unexplained fever were clinically diagnosed as FMF in this study. Low frequency but not pathogenic variants in genes other thanMEFVwere identified in 30.1% of the cases. It is not clear how much these gene variants contribute to the inflammatory phenotypes; therefore, further analysis would uncover their autoinflammatory phenotypes that cause fever.